1. Field of Invention
This invention relates to pulmonary therapy and ventilatory support of pulmonary function. In particular, the invention is directed to an aerosol delivery system and a ventilation circuit adaptor for pulmonary delivery of aerosolized substances and/or for other therapeutic and/or diagnostic purposes, in combination with noninvasive or invasive respiratory ventilation support.
2. Description of Related Art
Various patents, patent publications and scientific articles may be referred to throughout the specification. The contents of each of these documents are incorporated by reference herein, in their entireties.
Patients, both adult and infants, in respiratory failure or those with respiratory dysfunction are typically mechanically ventilated in order to provide suitable rescue and prophylactic therapy. Respiratory failure in adults or infants can be caused by any condition relating to poor breathing, muscle weakness, abnormality of lung tissue, abnormality of the chest wall, and the like. Additionally, pre- and full-term infants born with a respiratory dysfunction, such as respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPHN), acute respiratory distress syndrome (ARDS), pheumocystis carinii pneumonia (PCP), transient tachypnea of the newborn (TTN) and the like often require prophylactic or rescue respiratory support. In addition to respiratory support, infants suffering from, or at risk of RDS are often treated with exogenous surfactant, which improves gas exchange and has had a dramatic impact on mortality. Typically, the exogenous material is delivered as a liquid bolus to the central airways via a catheter introduced through an endotracheal tube. Infants born at 28 weeks or less are almost universally intubated and mechanically ventilated. There is a significant risk of failure during the process of intubation and a finite chance of causing damage to the upper trachea, laryngeal folds and surrounding tissue. Mechanical ventilation over a prolonged time, particularly where elevated oxygen tensions are employed, can also lead to acute lung damage. If ventilation and oxygen is required for prolonged periods of time and/or if the ventilator is not sufficiently managed, the clinical consequences can include bronchopulmonary dysplasia, chronic lung disease, pulmonary hemorrhage, intraventricular hemorrhage, and periventricular leukomalacia.
Infants born of larger weight or gestational age who are not overtly at risk of developing respiratory distress syndrome, or infants who have completed treatment for respiratory distress syndrome can be supported by noninvasive means. Attempts were made to administer liquid surfactant without intubation: to the posterior pharynx through the catheter, with spontaneously breathing infant [1], or to the pharynx through the laryngeal mask with transient positive pressure ventilation (PPV) [2]. Another non-invasive approach is nasal continuous positive airway pressure ventilation (nCPAP or CPAP). CPAP is a means to provide voluntary ventilator support while avoiding the invasive procedure of intubation. Nasal CPAP is widely accepted among clinicians as a less invasive mode of ventilatory support for preterm newborns with mild/moderate RDS. CPAP has been demonstrated to be effective in increasing functional residual capacity (FRC) by stabilizing and improving alveolar function [3], and in dilating the larynx [4]. Based on animal work, CPAP in combination with surfactant therapy has been also shown to minimize the risk for bronchopulmonary dysplasia (BPD) development among preterm baboons [5]. Randomized clinical trials focused on the use of nCPAP in the prophylaxis of RDS did show the benefit of nCPAP after instillation of surfactant via endotracheal tube [6, 7]. CPAP provides humidified and slightly over-pressurized gas (approximately 5 cm H2O above atmospheric pressure) to an infant's nasal passageway utilizing nasal prongs or a tight fitting nasal mask. CPAP also has the potential to provide successful treatment for adults with various disorders including chronic obstructive pulmonary disease (COPD), sleep apnea, acute lung injury (ALI)/ARDS and the like.
A typical ventilatory circuit for administering positive pressure ventilation includes a positive pressure generator connected by tubing to a patient interface, such as a mask, nasal prongs, or an endotracheal tube, and an exhalation path, such as tubing that allows discharge of the expired gases, e.g., to the ventilator or to an underwater receptacle as for “bubble” CPAP. The inspiratory and expiratory tubes are typically connected to the patient interface via a “Y” connector, which contains a port for attaching each of the inspiratory and expiratory tubes, as well as a port for the patient interface and, typically, a port for attaching a pressure sensor. In a closed system, such as with use of a tight-fitting mask or endotracheal tube, administration of other pulmonary treatment, e.g., pulmonary surfactant, or diagnosis generally requires temporary disconnection of the ventilatory support while the pulmonary treatment is administered or the diagnosis is conducted.
Recent efforts have focused on delivery of surfactant and/or other active agents in an aerosolized form, in order to enhance delivery and/or avoid or minimize the trauma of prolonged invasive mechanical ventilation. However, if the patient is receiving ongoing ventilatory support, administration of aerosolized active agents may necessitate interruption of the ventilatory support while the aerosol is administered. As a result, attempts have been made to deliver aerosolized active agents simultaneously with noninvasive positive pressure. For instance, Berggren et al. (Acta Pcediatr. 2000, 89:460-464) attempted to delivery pulmonary surfactant simultaneously with CPAP, but were unsuccessful due to the lack of sufficient quantities of surfactant reaching the lungs.
U.S. Patent publication 2006/0120968 by Niven et al. describes the concomitant delivery of positive pressure ventilation and active aerosolized agents, including pulmonary surfactants. Delivery was reported to be accomplished through the use of a device and system that was designed to improve the flow and direction of aerosols to the patient interface while substantially avoiding dilution by the ventilation gas stream. The system employed an aerosol conditioning chamber and a uniquely-shaped connector for directing the aerosol and the ventilation gas.
U.S. Pat. No. 7,201,167 to Fink et al., describes a method of treating a disease involving surfactant deficiency or dysfunction by providing aerosolized lung surfactant composition into the gas flow within a CPAP system. As shown in FIGS. 1 and 6 of the Fink et al. patent, the aerosol is carried by air coming from a flow generator wherein the aerosol is being diluted with the air.
Typically, a constant flow CPAP/ventilator circuit used for breathing support consists of an inspiratory arm, a patient interface, an expiratory arm and a source of positive end expiratory pressure (PEEP valve or column of water). Currently, aerosol generator manufacturers place nebulizers within the inspiratory arm of the CPAP/ventilator tubing circuit. This can potentially lead to aerosol dilution and decrease in aerosol concentration (see U.S. Pat. No. 7,201,167 to Fink et al.). Aerosol dilution is caused by much higher flows in the CPAP/ventilator circuit as compared to the peak inspiratory flow (PIF) of treated patients. Placement of the nebulizer between ‘Y’ connector and endotracheal tube (ET) or other patient interface as proposed by Fink et al. [11]account for significant increase in dead space depraving patient from appropriate ventilation.
To overcome the deficiencies of the prior art, the inventors developed a special adaptor which enables sufficient separation of the aerosol flow from the ventilation flow maintaining optimized ventilation as well as a novel aerosol delivery system.
All references cited herein are incorporated herein by reference in their entireties.